Genetic variants in nitric oxide synthase genes and the risk of male infertility in a Chinese population: a case-control study

PLoS One. 2014 Dec 17;9(12):e115190. doi: 10.1371/journal.pone.0115190. eCollection 2014.

Abstract

Background: In recent years, oxidative stress has been studied extensively as a main contributing factor to male infertility. Nitric Oxide, a highly reactive free radical gas, is potentially detrimental to sperm function and sperm DNA integrity at high levels. Thus, the aim of this study was to investigate the associations between five polymorphisms in nitric oxide synthase genes (NOSs) and the risk of male infertility and sperm DNA damage as well.

Methods: Genotypes were determined by the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using unconditional logistic regression.

Results: Our results revealed a statistically significant difference between the cases and controls in both genotypic distribution (P<0.001) and allelic frequency (P = 0.021) only for the NOS3 rs1799983 SNP. Multivariate logistic regression analyses revealed that rs1799983 was associated with a borderline significantly increased risk of male infertility (GT vs. GG: adjusted OR = 1.30, 95% CI: 1.00-1.70; GT+TT vs. GG: adjusted OR = 1.34, 95% CI: 1.03-1.74; P trend = 0.020). Moreover, NOS3 rs1799983 was positively associated with higher levels of sperm DNA fragmentation (β = 0.223, P = 0.044). However, the other 4 polymorphisms (NOS1 rs2682826, NOS1 rs1047735, NOS2 rs2297518, and NOS2 rs10459953) were not found to have any apparent relationships with male infertility risk.

Conclusions: Of five NOS gene polymorphisms investigated in the present study, we found NOS3 rs1799983 might cause oxidative sperm DNA damage, thereby contributing to male infertility.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • China / epidemiology
  • Follow-Up Studies
  • Humans
  • Infertility, Male / enzymology
  • Infertility, Male / epidemiology*
  • Infertility, Male / genetics*
  • Male
  • Nitric Oxide Synthase Type I / genetics*
  • Nitric Oxide Synthase Type II / genetics*
  • Nitric Oxide Synthase Type III / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Prevalence
  • Prognosis
  • Spermatozoa / chemistry
  • Spermatozoa / enzymology*
  • Young Adult

Substances

  • NOS1 protein, human
  • NOS2 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81202243, Grant No. 81172694 and Grant No. 30901210); the Natural Science Foundation of Jiangsu Province (Grant No. BK2012087); the practice innovation training program projects for the Jiangsu College students (2012JSSPTTP1018), the Jiangsu Province's Qinglan project (JX2161015124), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.